Abstract
Accumulation of radiolabelled monoclonal antibodies (mAb) in human B-lymphoma xenografts was found to result in two distinct patterns. The basic elements leading to these patterns were elucidated by autoradiographic and immunohistological analysis applied to the nude mouse xenografts BJAB and OCI.LY1. With BJAB, accumulation occurred exclusively in peripheral cell layers of the lymphoma nodule, while central areas were not accessible irrespective of mAb dose. This feature was the consequence of an inefficient transport across intratumoral vessels together with peripheral mAb supply through a subcapsular pseudosinus. With OCI.LY1, intratumoral vessels showed generalized leakiness. Furthermore, interstitial transport was operative to a fair extent, such that in early images multiple sites of mAb extravasation were obvious, which coalesced during the course of prolonged uptake. The pattern of peripheral mAb uptake resulted in a low overall tumour uptake, while multifocal uptake yielded substantial accumulation values.
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Cobb LM, Humphreys JA, Harrison A (1987) The diffusion of a tumour-specific monoclonal antibody in lymphoma infiltrated spleen. Br J Cancer 55: 53
Del Vecchio S, Reynolds JC, Carrasquillo JA, Blasberg RG, Neumann RD, Lotze MT, Bryant GJ, Farkas RJ, Larson SM (1989) Local distribution and concentration of intravenously injected 131I-9.2.27 monoclonal antibody in human malignant melanoma. Cancer Res 49: 2783
Epenetos AA, Nimmon CC, Arklie J, Elliott AT, Hawkins LA, Knowles RW, Britton KE, Bodmer WF (1982) Detection of human cancer in an animal model using radio-labelled tumour-associated monoclonal antibodies. Br J Cancer 46: 1
Fraker PJ, Speck JC (1980) Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3,6-diphenylglycoluril. Biochem Biophys Res Commun 80: 849
Fujimori K, Covell DG, Fletcher JE, Weinstein JN (1989) Modeling analysis of the global and microscopic distribution of immunoglobulin G, F(ab′)2, and Fab in tumors. Cancer Res 49: 5656
Fujimori K, Covell DG, Fletcher JE, Weinstein JN (1990) A modeling analysis of monoclonal antibody percolation through tumors: a binding-site barrier. J Nucl Med 31: 1191
Garcia CF, Lowder J, Meeker TC, Bindl J, Levy R, Warnke RA (1985) Differences in “host infiltrates” among lymphoma patients treated with anti-idiotype antibodies: correlation with treatment response. J Immunol 135: 4252
Jain RK (1989) Delivery of novel therapeutic agents in tumors: physiological barriers and strategies. JNCI 81: 570
Jain RK, Baxter LT (1988) Mechanisms of heterogeneous distribution of monoclonal antibodies and other macromolecules in tumors: significance of elevated interstitial pressure. Cancer Res 48: 7022
Matzku S, Bihl H, Moldenhauer G, Dörken B, Möller P (1989) Experimental approaches to tumor therapy with monoclonal antibodies. In: Cancer therapy. New trends. Bannasch P (ed.), Springer-Verlag, Heidelberg, p 219
Matzku S, Kirchgessner H, Schmid U, Temponi M, Ferrone S (1989) Melanoma targeting with a cocktail of monoclonal antibodies to distinct determinants of the human HMW-MAA. J Nucl Med 30: 390
Matzku S, Schmid J, Tilgen W (1990) Autoradiographic evaluation of monoclonal antibodies' access to melanoma-associated antigens in melanoma xenografts. J Invest Dermatol 95: 671
Pervez S, Epenetos AA, Mooi WJ, Evans DJ, Rowlinson G, Dhokia B, Krausz T (1988) Localization of monoclonal antibody AUA1 and its F(ab′)2 fragments in human tumour xenografts: an autoradiographic and immunohistochemical study. Int J Cancer [Suppl] 3: 23
Pezzutto A, Dörken B, Feller A, Moldenhauer G, Schwarz R, Wernet P, Thiel E, Hunstein W (1986) HD37 monoclonal antibody: a useful reagent for further characterization of “non-T/non-B” lymphoid malignancies. In: Leukocyte typing II. Reinherz EL, Haynes BF, Nadler LM, Bernstein ID (eds), Springer, Berlin Heidelberg New York, p 391
Pimm MV, Baldwin RW (1984) Quantitative evaluation of the localization of a monoclonal antibody (791T/36) in human osteogenic sarcoma xenografts. Eur J Cancer Clin Oncol 20: 515
Press OW, Farr AG, Borroz KI, Anderson SK, Martin PJ (1989) Endocytosis and degradation of monoclonal antibodies targeting human B-cell malignancies. Cancer Res 49: 4906
Sands H, Jones PL, Shah SS, Palme D, Vessella RL, Gallagher BM (1988) Correlation of vascular permeability and blood flow with monoclonal antibody uptake by human Clouser and renal cell carcinoma xenografts. Cancer Res 48: 188
Schmid U, Schirrmacher V, Bihl H, Matzku S (1990) Quantitation of antibody uptake in spontaneous metastases. Br J Cancer 62: 64
Trauth BC, Klas C, Peters AMJ, Matzku S, Möller P, Falk W, Debatin K-M, Krammer PH (1989) Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science 245: 301
Tweeddale ME, Lim B, Jamal N, Robinson J, Zalcberg J, Lockwood G, Minden MD, Messner HA (1987) The presence of clonogenic cells in high-grade malignant lymphoma: a prognostic factor. Blood 69: 1307
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Schmid, J., Möller, P., Moldenhauer, G. et al. Monoclonal antibody uptake in B-cell lymphomas: Experimental studies in nude mouse xenografts. Cancer Immunol Immunother 36, 274–280 (1993). https://doi.org/10.1007/BF01740910
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DOI: https://doi.org/10.1007/BF01740910